Genita herpes simplex virus (HSV) infection is one of the most common sexually transmitted diseases (STD) in the United States. These infections are conspicuous by their painful course, frequent recurrence, high contagiousness, and persistent latency. The most grave consequence of genital herpes is infection of infants born to mothers who are excreting virus at delivery. Infants exposed to HSV may contract an infection with an untreated mortality rate of 70%. Despite the problem of neonatal HSV infection, there is a paucity of data on the epidemiology of genital herpes during pregnancy. Most of the available data concerns the incidence of asymptomatic shedding of SHV in women with histories of genital HSV. A major limitation of these data is exemplified by the observation that 50% of neonates who contract HSV are born to women with neither current symptoms nor a past history of genital herpes. There is a clear need for more information regarding the epidemiology of this STD in pregnant women. Although 10-15% of genital herpes infections are caused by HSV-1, the remainder are caused by HSV-2. Therefore, the prevalence of genital herpes can be approximated by determining antibody to HSV-2. Extensive antigenic homology between HSV-1 and 2 proteins has interfered with the serologic distinction of past HSV-1 and 2 infections. Recently, the gG protein of HSV-2 (gG-2) has been demonstrated to have type specific epitopes. The nucleotide sequence of the gene specifying gG-2 has been elucidated. A monoclonal antibody to gG-2 provides the basis for an ELISA serologic assay which can be used to define the true prevalence of HSV-2 infections. A limitation of the current gG-2 ELISA method is that it is indirect, requiring multiple incubation steps to perform. Although this assay is sensitive and specific, it is time-consuming and costly. The assay would be simpler, more rapid, and less expensive if a source of gG-2 antigen were available which did not require immunoaffinity steps for preparation. Recombinant DNA cloning provides a means whereby specified gene products can be expressed in large quantities, free of other viral proteins and antigens. We propose to develop a simple and rapid assay for the serologic diagnosis of HSV-2 infection based upon recombinant DNA methods. We will clone the gG-2 sequences into a plasmid suitable for expression in a mammalian cell system and use this source of gG-2 in an assay to detect HSV-2 specific antibodies. The failure of antepartum cultures to predict asymptomatic shedding at delivery in women with past recurrent genital herpes along with the fact that many mothers of infants with neonatal HSV have no history of genital herpes requires another approach to the problem of neonatal HSV. We propose to investigate the value of performing HSV-2 specific serologic testing early and late in gestation. Past or recent HSV-2 infection will be determined by testing paired sera from the first prenatal visit and 28 weeks gestation. The frequency of HSV-2 infections in consecutive pregnant women with or without a history of genital HSV and the proportion which are primary infections will be assessed. Cultures will be obtained from all mothers and infants at delivery. The frequency of asymptomatic shedding of HSV at delivery among women with or without serologic evidence of past or recent HSV-2 infections will be determined. The frequency of prematuity, low birth weight, and/or evidence of intrauterine HSV infections among neonates born to mothers with serologic evidence of HSV-2 infections will be assessed. Much of the continued morbidity and mortality of neonatal HSV is due to delayed diagnosis. While delivery cultures will not prevent the exposure of infants to asymptomatic maternal HSV, identification of exposed infants should allow early diagnosis and immediate therapy.
